There exists an unmet clinical need and widespread research interest to better understand the dose- concentration-response and adverse events relationships of immunosuppressive medications in transplant patients. The pediatric transplant community is missing a significant opportunity to optimize outcomes by focusing predominantly on trough concentrations and the area under the curve (AUC) of the blood concentrations as the most important parameters to correlate with empirical evidence of rejection. This application focuses on the development of mechanism based pharmacokinetic-pharmacodynamic (PK-PD) models that characterize the full concentration-effect relationship of immunosuppressive drugs on validated effect and clinical outcome measures. The structural PK-PD models will allow correlation of response and surrogate immunology biomarkers with computed concentrations at the target site. The proposed PPRU network study is designed to address the current information gap regarding age dependent disposition of mycophenolate mofetil (MMF, CellCept[unreadable]) in pediatric renal transplant recipients and its potential impact on the exposure-response and toxicity relationships. In this application, research, advanced learning and mentoring agendas are formulated to describe the added value of the K24. The research agenda includes a population PK-PD study in pediatric kidney transplant patients. Particular attention is paid to the role of the K24 in facilitating secondary analyses particularly using biomarkers (Inosine Monophosphatase Dehydrogenase inhibition, CD25 expression and mitogenesis) for indirect response modeling. These models will serve to optimize therapy for each child. These analyses coupled with trial simulation can better predict research outcomes and rationalize trial design using biomarker and outcome data of the PK-PD study. The core PK-PD content illustrated by the MMF model has broad application in pediatric care and offers a paradigm to launch similar studies and mentoring opportunities across disciplines. The Pi's advanced learning agenda therefore is focused in mechanism based modeling and clinical trial simulation. The Pi's leadership in pediatric clinical pharmacology will serve the mentoring agenda and energize an accredited Clinical Pharmacology Program which the PI leads. Taken together, the research, advanced learning, and mentoring agendas synergize to promote practical and theoretical contributions to the optimization of drug studies for better treatment of MMF in pediatric transplant and pediatric care broadly.